HEMOLYTIC DISEASE OF THE NEW BORN HDN, CAUSES, SYMPTOMS, DIAGNOSIS, OTHERS

  Introduction

Hemolytic disease of the new born or Blood Group Incompatibility occur when fetal red blood cell (RBC) which possess an antibody which the mother does not have crosses the placenta into maternal circulation where they stimulates antibody production, the antibody returns to the fetal circulation  and cause destruction of red blood cells.

The new red blood cells called Erythroblastosis are often immature red blood cells and cannot do the work of normal red blood cells and are therefore broken down, and as they break down, a substance called Bilirubin is formed. Babies are not easily able to eliminate Bilirubin and it builds up in the blood and tissue flood of the baby’s body, a condition known as HYBER BILIRUBIN (excess bilirubin). Bilirubin has a pigment or coloring that causes yellowing of the skin, eyes and tissues a condition called JAUNDICE.

Normally HDN causes still births or miscarriages, but if the baby survive they usually suffers a range of  medical conditions such as enlarged liver and spleen, edema, Kernicterus and heart failure, alongside jaundice, all of which are not easily treated but easily avoided.

One factor, the Rh Factor, is what determines the risk of this disease, Rh factor is a kind of protein present on the surface of the red blood cell and it is important in helping the body distinguish its own blood from that of another person.

Its necessary that the individual know their Rh type by going for blood testing and avoid incompatible  partners so as to avoid this disease of infant after all no one wants to have any child with a severe medical condition.

       HEMOLYTIC DISEASE OF THE NEW BORN (HDN)

Hemolytic disease of the new born also known as Erythroblastosis or Blood Group Incompatibility occur when fetal red blood cell  (RBC) which possess an antibody which the mother does not have crosses the placenta into maternal circulation where they stimulates antibody production, the antibody returns to the fetal circulation  and begins to destroy red blood cells.

In other word, HDN, is an autoimmune condition which develops in a fetus when Immunoglobulin Molecule (IgG) one of the five main types of antibody produced by the mother passes through the placenta.

Among these antibodies are some which attack the red blood cells in the fetal circulation, the Red blood are broken down and the fetus develops Recticulocytosis and Anemia. This disease of the new born ranges from mild to severe and death from heart failure (Hydrop fetalis) can occur.

The new red blood cells called Erythroblastosis are often immature red blood cells and cannot do the work of normal red blood cells and are therefore broken down, and as they break down, a substance called Bilirubin is formed. Babies are not easily able to eliminate Bilirubin and it builds up in the blood and tissue flood of the baby’s body, a condition known as HYPER BILIRUBIN (excess bilirubin). Bilirubin has a pigment or coloring that causes yellowing of the skin, eyes and tissues a condition called JAUNDICE.

When this disease is mild or severe, many Red blood cells are present in in the fetal blood, hence it is called Erythroblastosis.

In severe HDN, the unborn baby cells cannot carry any oxygen because of the destruction of red blood cells (anemia) and the baby dies of heart failure (Hydrop fetalisis). This explains by fetuses affected by these diseases may be miscarried or may be still born.

Most babies born with HDN, are either healthy or have mild anemia that can be easily treated.

 

HDN affects the second baby; it rarely affects the first pregnancy. However, it may affect any other RHD+ fetuses. 

About 85% of people are Rh positive(Rh+) while the remaining 25%  Rh negative. (Rh-), simply means Rhesus factor, by definition, it’s a kind  of protein that is either present or absence on the surface of  Red blood cells.

Rh factor helps the body to distinguish its blood from the blood of another person.

It is a blood group system named after Rhesus monkey because they were first used in the research to make antiserum for typing blood sample, if the Anitserum  agglutinate your red blood cells you are Rh+ but if it does not you are Rh-..

Gene comes in pairs, Recessive and Dominant, the Rh- gene is recessive, i.e they do not occur in identical pairs, (Heterozygous), while the Rh+ gene is dominant i.e identical ( \Homozygous). 

Gene can only express itself or produce phenotype character when the Alleles are identical (Homozygous) . This means that there is a greater than or equal to 50% chances that an Rh- mother will conceive and have an RhD+ baby if the father is RhD+.

Each child has a to 50 to 50% chances of being either Rh- or Rh+. However, if the father has two RhD+ gene, all babies born to that couple will be RhD+.

In summary, HDN is caused by mother fetus incompatibility that is when the mother s Rh- (dd) and the unborn baby is Rh+ (DD or Dd).

 CAUSES OF HDN

Antibodies are produced when the body is exposed to an antigen foreign to the makeup of the body. If a mother is exposed to a foreign antigen and it produces IgG as opposed to IgM which does not cross he placenta, the IgG will target the antigen, if present in the fetus may affect it in the uterus and persist after delivery.

There are three most common models in which a woman become sensitized or produces IgG antibodies against a particular antigen.

   Fetal maternal Hemorrhage: This occurs due to child’s birth, abortion, trauma, rupture in the placenta during delivery and breach in the uterine wall. In subsequent pregnancy if there if there is similar incompatibility in mother / fetus blood, these antibodies are then able to cross the placenta into the fetal blood stream to attach to the red blood cells and cause hemolysis, in other words, if a mother has an RhD (D being the major rhesus factor), IgG antibodies as a result of previously carrying an RhD positive fetus, this antibody will only affect a fetus with RhD positive blood.

    - The woman may have received a therapeutic blood transfusion, ABO blood group system and D antigen of rhesus blood group system. Typing is routine prior to transfusion.

   - The third sensitization model can occur in women of blood type O, the immune response to antigen A and B antigens that ae wide spread in the environment, usually lead to production of IgM ant A and IgG anti B antibodies early in life. On rear occasion IgG antibodies are produced.

    Symptoms of HDN

          Symptoms of HDN expressed in pregnancy (fetus) differ from the symptoms experienced after birth.

          The after birth symptoms of HDN includes the followings.

1. Jaundice (hyperbilirubinemia): This is the yellow coloring of the amniotic fluid, umbilical cord, skin and eye. The baby may not look yellow immediately after birth but jaundice can develop quickly within 24-38hours.

2. Kernicterus: when hyperbilirubinemia is sever, it result in buildup of bilirubin in the brain, this can cause seizure, brain damage, deafness and eventually death.

3. Hydrop Fetalis: This can occur as a result of the inability of the red blood cells to carry oxygen to the heart, the baby therefore develop difficulties in breathing and heart begins to fail, also the baby develop(edema) swelling and become extremely pale due to buildup of fluid in the baby’s organ and tissue.

     Symptoms of HDN in fetus (pregnancy) includes the following.

- The ultrasound of the fetus may show enlarge liver spleen or heart failure and buildup of fluid in the abdomen.

- Amniocentesis: The amniotic fluid may show yellow coloring and contain bilirubin.

DIAGNOSIS OF HDN

       The diagnosis of HDN requires the following methods.

a. Antibody liter and past history of HDN: Up to 1961, antibody liter and past history of HDN in various pregnancies where the only parameters available to predict the severity of HDN before delivery. Although both of these parameters determine the need for further and more potentially more invasive measures by themselves, they are only 62% accurate in predicting severity of HDN.

b. Invitro cell mediated maternal function assays: This method involves determining the building (avidity) of antibody for antigen on the red cell membrane and its ability to lyses affected red blood cells (Bowman 1996).

c. Amniotic fluid spectrophotometry: This first definitive investigation procedure was initially reported by Bevis, Amniotic fluid spectrophotometry was described by Lileg in 1961. Measurement from deviation at linearity at 450nm, the wave length at which bilirubin absorb light, the AO.D 450 was a major advance in predicting hemolytic disease of the newborn, (Bowman 1996).

d. Perinatal Ultrasonography: The development of ultrasound techniques (us) in the late 1970’s has improved the diagnosis of HDN. With ultrasound one can make the diagnosis of hydrops (asertes, edema, pleural and pericardia effusions) but unfortunately one cannot make the diagnosis of impending hydrops. Ultrasound is very useful in reducing the risk of placenta trauma at amniocentesis and in directing the needle to both intra peritoneal (IPT), and intravascular fetal transfusion (IVT) After IPT, ultrasound confirms the presence of blood in the peritoneal cavity and serial examination monitor its absorption. At IVT, ultrasound observation of turbulence within the umbilical vessel as the blood is injected confirms that it is being injected into the fetal circulation, after fetal transfusion, ultrasound biophysical scoring provides an accurate assessment of the fetal condition.

e. Fetal blood sampling: This method measures all blood parameters; it is very useful in detecting HDN in the absence of hydrops. The procedure is relatively begin, carrying a fetal mortality rate of less than 1% since it carries with it a great likelihood of tetromaternal hemorrhage. It should be used only amniotic fluid AOD 45O reading indicates a fetus at risk or when an anterior placenta produces amniocentesis and the maternal history and or maternal antibody liter indicates fetuses at risk. Fetal blood sampling may be possible at 17 – 18 weeks but it is only feasible at 18 - 20.

Treatment of HDN

There are two options of treatment of HDN, before birth option and after birth options.

Before birth options include intrauterine or early induction of labour when pulmonary maturity has been attained. The mother may also undergo plasma exchange to reduce the level of circulating antibody by as much as 70%.

After birth options depend on severity of the condition but could include

-   Temperature stabilization and monitoring

-   Photo therapy

-   Transfusion with compatible red blood cells

-   Exchange transfusion with blood type compatible with both more and infant.

- Sodium carbonate for correction of acidosis and or assisted ventilation.

Rh positive mothers who have had a pregnancy with or are pregnant with Rh positive babies are offered Rh immune globin G (RhIG) at 22weeks during pregnancy, at 34weeks, and within 72hours after delivery to prevent sensitization to the D antigen. It works by binding any fetal red blood cell with the D antigen before the mother is able to produce an immune respond and develop anti-D IgG.

A draw back to partum administration of RhIG, is that it causes a positive antibody screen where the mother is tested, which can be difficult to distinguish from natural immunological response that results in antibody production.

Erythropoietin treatment can also be used as it prevents as it prevents any further agglutination.

Management of HDN

a -Preparation prior to delivery: for severe anemia, type O RH negative packed RBCs cross match against the mother, there should be blood in resuscitation room to correct anemia immediately after birth by Partial Exchange Transfusion (EXTX). 

   There should be surfactants if the infant is preterm, catheter e,g angiocath for immediate drainage of hydropic fluid.

 

  - Resuscitation: The major problem at birth are cardiopulmonary and relates to effect of severe anemia, hydrops and prematurity,  because of the several problems with HDN, effective resuscitation involves many individuals.

Prevention of HDN

At the time of booking, (12 - 16weeks), every pregnant woman should have a blood sample sent for determination of ABO and RhD group and testing for red blood cells alloantibodies which may be detected against parental blood group antigen.

Where a clinically significant antibody capable of causing HDN particularly Anti D or anti K, is present in a maternal blood sample, determining the fathers phenotype produce useful information to predict the likelihood of the fetus carrying the relevant red cell antigen.  The complexity of paternal testing and the complexity of misidentification of the father need to be acknowledged.

-Routine anti natal prophylaxis should be done at 28 and 34 weeks.

-Therapeutic termination of pregnancy, all sensitized RhD negative mothers, should have medical or surgical terminations of pregnancy regardless of gestation.

-Patients with severe HDN should be referred to specialist units for monitoring and management.

RECOMMENDATIONS

Due to the severity of HDN and the high risk associated with treatment and the huge financial burden, the medical condition should be prevented through the followings,

-  Women and girls of child bearing age should not be given a transfusion with Rhc- positive blood or kell positive blood to avoid possibilities of sensitization.

-  All women and girls of child bearing age should go for blood testing so as to determine their Rh status, positive or negative and avoid incompatible male.

-  All men should go for blood testing so as to know their Rh status and help protect women from having babies with HDN by avoiding incompatible female.

-  Female population should be screened and all Rh negatives should be treated (immunized) by vaccination with Rh immunoglobulin (RhIgM) against sensitization to the antigen.

- HDN pregnancies should be terminated regardless of gestation period.

DEFINITIONS OF TERMS
Erythroblastosis:-The presence of large amount of erythroblast in the blood

Jaundice:-Yellowish coloration of the intergument, sclerae, and deeper tissue  and the excretion of bile pigments.

Antibody:-Immunoglobulin molecule with specific amino acid sequence evolved in man or other animals by an antigen and characteristic by reacting in a specific way.

Antibody:-Any substance that induces sensitivity when it comes in contact with the appropriate cells.

Bilirubin:-This is a yellowish coloration pigment produced by bile, its formed from Hemoglobin ( oxygen carrying pigment of the blood), during the breakdown of res blood cells (erythrocytes).

Bilirubinemia:-The present of small quantity of bilirubin in the blood.

Hydrops :-Excessive accumulations of  fluid in any part of the body or tissue.(SYN) Edema.